title: Impact of renin-angiotensin system in hepatocellular carcinoma.
abstract: Angiogenesis is a complex and critical process essential for supporting the growth of hepatocellular carcinoma (HCC) as well as hepatocarcinogenesis. Recent studies have revealed that renin-angiotensin system (RAS) is involved in many types of cancer including HCC. Some studies have proven that suppression of angiotensin-II (AT-II) by a clinically used angiotensin-converting enzyme inhibitor (ACE-I) significantly attenuated the HCC growth and hepatocarcinogenesis along with down-regulation of a potent angiogenic factor; namely, the vascular endothelial growth factor (VEGF). When used in combination with the clinical available drugs such as interferon (IFN) and vitamin K (VK), ACE-I exerted more potent anti-tumor activities as compared with either single agent in addition to suppression of the intra-tumoral angiogenesis both in experimental models and clinical practice. It is well known that AT-II plays an important role in the insulin resistance (IR), and IR is reportedly involved in the progression of HCC. The combination of ACE-I and branched-chain amino acids (BCAA) exerted a marked chemopreventive effect against HCC under the condition of IR. In addition to AT-II, aldosterone (Ald), which plays a role in the downstream of AT-II, is also involved in the HCC development, and a clinically used selective Ald blocker (SAB) significantly suppressed the HCC growth and hepatocarcinogenesis. Since ACE-I, IFN, VK, BCAA, and SAB are already in widespread clinical use without any serious adverse effects, they may represent a potential new strategy for cancer therapy and chemoprevention against HCC especially in combination with other angiostatic agents.
authors.affiliation: Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Shijo-cho 840, Kashikan, Nara 634-8522, Japan. yoshijih@naramed-u.ac.jp
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yoshiji
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Noguchi
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Ikenaka
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kaji
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Aihara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukui
mesh_terms: D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II